ArticleJournal of virology2006
Plasmid DNA sequences present in conventional herpes simplex virus amplicon vectors cause rapid transgene silencing by forming inactive chromatin.
Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Non-replicative herpes simplex virus genomic and amplicon vectors for gene therapy - an update.Gene therapy · 2025Review
- Improving cell and gene therapy safety and performance using next-generation Nanoplasmid vectors.Molecular therapy. Nucleic acids · 2023Review
- Genetic and Molecular Quality Control of Genetically Engineered Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing.Nature communications · 2022Article
- Innovative nonviral gene delivery strategies for engineering human mesenchymal stem cell phenotypes toward clinical applications.Current opinion in biotechnology · 2022Review
- Improvement of HSV-1 based amplicon vectors for a safe and long-lasting gene therapy in non-replicating cells.Molecular therapy. Methods & clinical development · 2021Article
- Reduced Heterochromatin Formation on the pFAR4 Miniplasmid Allows Sustained Transgene Expression in the Mouse Liver.Molecular therapy. Nucleic acids · 2020Article
- Efficient and Reproducible Multigene Expression after Single-Step Transfection Using Improved BAC Transgenesis and Engineering Toolkit.ACS synthetic biology · 2020Article
- Gene Therapy Tools for Brain Diseases.Frontiers in pharmacology · 2019Review
- Herpes Simplex Virus Vectors for Gene Transfer to the Central Nervous System.Diseases (Basel, Switzerland) · 2018Review
- RNAi-mediated knockdown of mouse melanocortin-4 receptor in vitro and in vivo, using an siRNA expression construct based on the mir-187 precursor.Experimental animals · 2017Article
- Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The capacity of target silencing by Drosophila PIWI and piRNAs.RNA (New York, N.Y.) · 2014Article
- A Site-Specific Integrated Col2.3GFP Reporter Identifies Osteoblasts Within Mineralized Tissue Formed In Vivo by Human Embryonic Stem Cells.Stem cells translational medicine · 2014Article
- Analysis of human embryonic stem cells with regulatable expression of the cell adhesion molecule l1 in regeneration after spinal cord injury.Journal of neurotrauma · 2014Article
- Differential type I interferon-dependent transgene silencing of helper-dependent adenoviral vs. adeno-associated viral vectors in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Suicidal gene therapy in the effective control of primary human hepatocellular carcinoma as monitored by noninvasive bioimaging.Gene therapy · 2012Article
- Mc-hES, a novel plasmid carrying human endostatin gene, inhibits nasopharyngeal carcinoma growth.Cancer gene therapy · 2012Article
- Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors.Current gene therapy · 2011Review
- Site-specific integrase-mediated transgenesis in mice via pronuclear injection.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The herpes simplex virus (HSV)-based amplicon vector, a bacterial-viral-mammalian cell shuttle system, holds promise as a versatile gene delivery vehicle because of its large transgene capacity. However, amplicon-mediated transgene expression is often transient. We hypothesized that the presence of prokaryotic DNA sequences within the packaged vector genome can trigger transcriptional silencing of the entire vector sequence. To test this, we constructed a novel amplicon vector devoid of bacterial sequences (minicircle [MC] amplicon). Although the same dose of the minicircle amplicon vector in normal human fibroblasts resulted in an expression of luciferase approximately 20 times higher than that caused by the conventional amplicon vector, no significant difference was observed in copy numbers of luciferase DNA between MC amplicon- and control-transduced cells. Quantitative analyses of levels of luciferase mRNA revealed that differential expression of luciferase was controlled at the transcriptional level. Chromatin immunoprecipitation PCR analyses of several regions of vector genomes revealed that the bacterial sequences found in the conventional amplicon DNA were associated with an inactive form of chromatin immediately after infection. The presence of bacterial sequences also affected the remaining vector sequences in the conventional amplicon vector. Finally, nude mice injected with the MC amplicon exhibited higher and more sustained expression of luciferase than those injected with the conventional amplicon, confirming the usefulness of the MC amplicon devoid of bacterial sequences. Although additional improvements are absolutely required, these findings are a significant first step toward developing a novel HSV amplicon vector that can achieve enhanced long-term transgene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.